In Silico Study of the Inhibitory Effect of Isoflavones on the Genes Frequently Reported in the Pathophysiology of Breast Cancer
Abstract
Abstract Views: 135
Phytoestrogens are naturally occurring plant-derived active substances found in a wide variety of foods. Numerous health benefits of phytoestrogens include the reduced occurrence of breast tumors. Overexpression of the protein serine-hydroxyl-methyl-transferase-2 (SHMT2) has been reported in breast cancer. In one-carbon metabolism SHMT2 enzyme is present, which is necessary for cancer cell proliferation in a low glucose environment. Hence, this study focused on natural isoflavones that have a toxic effect on the development of breast cancer cells without harming normal cells. The structure of the protein SHMT2 was retrieved from the protein data bank and the structure of isoflavones was determined using the PubChem database. The docking of isoflavones with SHMT2 was done to determine their inhibitory effect on the latter since it causes the rapid development of breast cancer cells. It was identified that two isoflavones (6O-acetyldaidzin and malonyldaidzin) have a high affinity to bind with the protein because of hydrogen bonding. This study highly recommends conducting clinical trials on human beings based on the interaction between phytochemicals and SHMT2 gene to determine the safe dosage level of the former.
Downloads
References
Křížová L, Dadáková K, Kašparovská J, Kašparovský T. Isoflavones. Molecules. 2019;24(6):1076. https://doi.org/10.3390/molecules24061076
Salinas CM, López-Sobaler AM. Benefits of soy in women's health. Nutr Hosp. 2017;34(Suppl 4):36-40. https://doi.org/10.20960/nh.1569
Soomro R, Faridi S, Khurshaidi N, Zahid N, Mamshad I. Age and stage of breast cancer in Pakistan: An experience at a tertiary care center. J Pak Med Assoc. 2018;68(11):1682-1685.
Hwang KA, Choi KC. Anticarcinogenic effects of dietary phytoestrogens and their chemopreventive mechanisms. Nutr Cancer. 2015;67(5):796-803. https://doi.org/10.1080/01635581.2015.1040516
Messina M. Soy and Health Update: evaluation of the clinical and epidemiologic Literature. Nutr. 2016;8(12):754. https://doi.org/10.3390/ nu8120754
Ward EM, DeSantis CE, Lin CC, et al. Cancer statistics: Breast cancer in situ. CA Cancer J Clin. 2015;65(6):481-495. https://doi.org/10.3322/ caac.21321
Zhang L, Chen Z, Xue D, et al. Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker. Oncol Rep. 2016;5112(36):2489-2500. https://doi.org/10.3892/ or.2016.5112
Bernhardt S, Bayerlová M, Vetter M, et al. Proteomic profiling of breast cancer metabolism identifies SHMT2 and ASCT2 as prognostic factors. Breast Cancer Res. 2017;19(1):1-4. https://doi.org/10.1186/s13058- 017-0905-7
Ning S, Ma S, Saleh AQ, et al. SHMT2 Overexpression Predicts Poor Prognosis in Intrahepatic Cholangiocarcinoma. Gastroenterol Res Pract. 2018;2018:4369253.
Newman AC, Maddocks ODK. One-carbon metabolism in cancer. Br J Cancer. 2017;116(12):1499-1504. https://doi.org/10.1038/bjc.2017.118
Minton DR, Nam M, McLaughlin DJ, et al. Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs. Mol Cell. 2018;69(4):610-621.e5. https://doi.org/10.1016/j.molcel.2018.01.024
Woo CC, Chen WC, Teo XQ, Radda GK, Lee PT. Downregulating serine hydroxymethyltransferase 2 (SHMT2) suppresses tumorigenesis in human hepatocellular carcinoma. Oncotarget. 2016;7(33):53005- 53017. https://doi.org/10.18632/oncotarget.10415
Tutunchi H, Naeini F, Ostadrahimi A, Hosseinzadeh-Attar MJ. Naringenin, a flavanone with antiviral and anti-inflammatory effects: A promising treatment strategy against COVID-19. Phytother Res. 2020;34(12):3137-3147. https://doi.org/10.1002/ptr.6781
Justulinjr L, Santos SAA, Damasceno DC. Nutrition and Prostate Cancer Prevention. Nutrition and Cancer Prevention: From Molecular Mechanisms to Dietary Recommendations. 2019;21(5):392. https://doi.org/10.1039/9781788016506-00392
Uifălean A, Schneider S, Gierok P, Ionescu C, Iuga CA, Lalk M. The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach. Int J Mol Sci. 2016;17(9):1443. https://doi.org/10.3390/ijms17091443
Ziaei S, Halaby R. Dietary Isoflavones and Breast Cancer Risk. Medicines (Basel). 2017;4(2):18. https://doi.org/10.3390/ medicines4020018
Iqbal J, Abbasi B, Khalil A, et al. Dietary isoflavones, the modulator of breast carcinogenesis: Current landscape and future perspectives. Asian Pac J Trop Med. 2018;11(3):186.
Uifălean A, Schneider S, Ionescu C, Lalk M, Iuga CA. Soy Isoflavones and Breast Cancer Cell Lines: Molecular Mechanisms and Future Perspectives. Molecules. 2015;21(1):E13. https://doi.org/10.3390/ molecules21010013
Zhang X, Cook KL, Warri A, et al. Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats. Clin Cancer Res. 2017;23(3):814-824.
Iqbal J, Abbasi BA, Mahmood T, et al. Plant-derived anticancer agents: A green anticancer approach. Asian Pac J Trop Biomed. 2017;7(12):1129-1150. https://doi.org/10.1016/j.apjtb.2017.10.016
Abotaleb M, Samuel SM, Varghese E, et al. Flavonoids in Cancer and Apoptosis. Cancers. 2018;11(1):2109-30. https://doi.org/10.1002/ptr.6155
